Researchers at the University of North Carolina (UNC) at Chapel Hill School of Medicine report that they have uncovered the genetic architecture controlling the growth of the collateral circulation, the back-up blood vessels that can provide oxygen to starved tissues in the event of a heart attack or stroke.
The results, published in the August 20 issue of Circulation Research, are reportedly the first to pinpoint a portion of the genome associated with variation in the density and diameter of collateral vessels. The paper is titled "Genetic Architecture Underlying Variation in Extent and Remodeling of the Collateral Circulation."
"This has really been the holy grail in our field, how to get new collaterals to form in a tissue with few in the first place," comments senior study author, James E. Faber, Ph.D., professor of cell and molecular physiology at UNC. "Our thesis has been that if we can figure out how these endogenous bypasses are formed in the first place in healthy tissues, what mechanisms and genetic pathways drive this, and why collaterals abundance varies so widely in healthy individuals, then we may have our answer."
The research, conducted in animal models, combined classical genetic mouse crosses with a technology called association mapping to identify the section of DNA involved, starting with the whole genome, narrowing it down to several hundreds of genes, and finally landing on nine candidates on mouse chromosome 7. The scientists concluded that collateral extent and remodeling are unique, highly heritable complex traits, with one quantitative trait loci predominantly affecting native collateral number and diameter.
The researchers are now looking at these genes to see if any one of them is responsible for variation in collateral formation. Dr. Faber says they also cannot discount the possibility that it is not genes that are the deciding factor, but rather regulatory DNA or RNA elements that also reside in that same section of the genome.
Either way, Dr. Faber hopes they can discover a sequence that could one day be used to predict who is most likely to develop a severe heart attack, stroke, or peripheral limb disease so those individuals can either modify their lifestyle or receive collaterogenic drugs to acquire new and potentially life-saving collateral vessels.